CN102531830B - Cis-1-halo-2-chloroalkene and preparation method and application thereof - Google Patents
Cis-1-halo-2-chloroalkene and preparation method and application thereof Download PDFInfo
- Publication number
- CN102531830B CN102531830B CN2012100047579A CN201210004757A CN102531830B CN 102531830 B CN102531830 B CN 102531830B CN 2012100047579 A CN2012100047579 A CN 2012100047579A CN 201210004757 A CN201210004757 A CN 201210004757A CN 102531830 B CN102531830 B CN 102531830B
- Authority
- CN
- China
- Prior art keywords
- cis
- chloro
- substituted
- colourless liquid
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- MTXPCGBRAHVXLY-VURMDHGXSA-N Cl/C=C(/C1=CCCCC1)\Cl Chemical compound Cl/C=C(/C1=CCCCC1)\Cl MTXPCGBRAHVXLY-VURMDHGXSA-N 0.000 description 1
- OQGSCHGFHOSXFY-VURMDHGXSA-N Cl/C=C(/c1ccccc1)\Cl Chemical compound Cl/C=C(/c1ccccc1)\Cl OQGSCHGFHOSXFY-VURMDHGXSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a cis-1-halo-2-chloroalkene compound. The compound has a constitutional formula I in the description. The invention also provides a selective synthesis method for the cis-1-halo-2-chloroalkene and the application of the cis-1-halo-2-chloroalkene in the synthesis of multi-substituted aromatic hydrocarbon, the preparation of Z-trisubstituted alkene and the synthesis of Z-trisubstituted alkene-containing medical intermediate and natural product. On the basis, the inventer achieves a new vitamin A synthesis route. By means of selective implementation, the invention increases the atom economy of chemical reaction, is easy to operate, is environment-friendly, and has high practical value.
Description
Technical field
The present invention relates to the field of chemical synthesis, be specifically related to a kind of cis-1-halogen-2-chloro-alkenes and its preparation method and application.
Background technology
Polysubstituted Olefins extensively exists in the natural product such as VITAMIN, prostaglandin(PG), insect pheromone and medicine and chemical intermediate, therefore, the synthetic of Polysubstituted Olefins is one of vitochemical important content, wherein, regio-and stereo-selectivity ground synthesizes Polysubstituted Olefins very challenging problem especially.
Synthetic following a, b and tri-kinds of approach of c of generally comprising of existing Polysubstituted Olefins:
Although Wei Dixi (Wittig) reaction and olefin metathesis reaction are still helpless for cis-disubstituted olefin, cis-tri-replacement or cis-tetra-substituted olefine preferably for synthesizing of some trans double bond.In recent years, developed in the world one and set out through the method (approach c) of twice synthetic Polysubstituted Olefins of cross-coupling reaction from 1,2-dihaloalkene, obviously, synthetic new approaches that provide of Polysubstituted Olefins are provided for this.
But continuously the prerequisite of cross-coupling reaction method is the cis-1 that can provide pure, 2-dihaloalkene or trans 1,2-dihaloalkene.And at present for 1, mainly prepared by the electric halogenating reaction of alkynes parent by the synthetic of 2-dihaloalkene:
This reaction is through being similar to halogen father-in-law ion intermediate, the halogen ion from the negative attack obtain corresponding 1, the 2-dihaloalkene, so often obtain with anti-form-1, the 2-dihaloalkene is main mixture.In this mixture, cis-trans-isomer polarity is very approaching, is effectively separated chemically being difficult to, so cis-1, the selectivity of 2-dihaloalkene is synthetic extremely important.Therefore, be necessary to study cis-1, the effective ways that the stereoselectivity of 2-dihaloalkene is synthetic, thus the natural product that contains the Polysubstituted Olefins structural unit and the synthetic effective way that provides of medicine intermediate are provided.
Summary of the invention
(have another name called: the chloro-2-substituting group-ethene of cis-1-halogen-2-), this cis-1-halogen-2-chloro-alkenes can or contain the synthetic effective way that provides of pharmaceutical intermediate and the natural product of three substituted olefine structural units for polysubstituted aromatic hydrocarbons, Z-tri-substituted olefines to the invention provides a kind of cis-1-halogen-2-chloro-alkenes.
The present invention also provides the preparation method of a kind of cis-1-halogen-2-chloro-alkenes, and simple to operate and environmental protection can optionally obtain cis-1-halogen-2-chloro-alkenes.
A kind of cis-1-halogen-2-chloro-alkenes is the compound shown in structural formula I:
In the structural formula I, R is phenyl, monosubstituted phenyl, di-substituted-phenyl, tri-substituted phenyl, 1-naphthyl, 2-naphthyl, thienyl, furyl, thiazolinyl, styryl, benzyloxy methylene radical, alkyl or heteroatoms substituted alkyl etc.;
X is chlorine atom or bromine atoms;
Substituting group on described monosubstituted phenyl, di-substituted-phenyl or tri-substituted phenyl is alkyl, alkoxyl group, fluorine atom, chlorine atom or bromine atoms; Substituting group on di-substituted-phenyl or tri-substituted phenyl can be the same or different.
In compound shown in described structural formula I, three substituted olefine stereochemistry are cis, and namely two halogen atoms are at two key homonymies.
In order to reach better invention effect, preferably:
Described thiazolinyl is C
2-C
20A kind of in alkylene;
Described alkyl is C
1-C
20Alkyl in a kind of;
Described heteroatoms substituted alkyl is the C that N, S, P or O heteroatoms replace
1-C
20Alkyl in a kind of;
Described alkoxyl group is C
1-C
20Alkoxyl group in a kind of.
The present invention finds: the proton solution reaction of palladium catalysis can be cis-1, and the 2-dihaloalkene provides effective way, and diagram is as follows:
By research, the present invention finds that additive is that the introducing of the connection alkene ester shown in formula II is conducive to the carrying out reacted.Next, the present invention studies in detail the catalyzer of this reaction, finds that palladium has provided best effect.Then, other conditions such as the solvent of this reaction and halogen ion source are studied, have obtained the preparation method of the cis of following optimization reaction conditions-1-halogen-2-chloro-alkenes:
The preparation method of described cis-1-halogen-2-chloro-alkenes comprises step:
Palladium and lithium chloride are dissolved in acetic acid, add the connection alkene ester shown in the compound shown in formula II I and formula II as reaction system, 40 ℃-60 ℃ react completely after, make cis-1-halogen-2-chloro-alkenes;
Reaction in the present invention, its reaction times does not have strict restriction, by timing sampling, carries out trace analysis by existing analytical procedure such as tlc (TLC), all reacts complete when wherein a kind of raw material or plurality of raw materials, and the terminal that is considered as reacting gets final product.
Through overtesting, in order to make reaction, to carry out fully, the described reaction times was generally 4 hours-6 hours.
As preferably:
The mol ratio of the compound shown in described palladium and formula II I is 0.02-0.05: 1.
The mol ratio of the compound shown in the connection alkene ester shown in described formula II and formula II I is 0.1-0.3: 1, and more preferably 0.2: 1.
The mol ratio of the compound shown in described lithium chloride and formula II I is 1-2: 1.
The 60 ℃ of temperature of reaction of take are example, and diagram is as follows:
The compound that described cis-1-halogen-2-chloro-alkenes can be used for preparing polysubstituted aromatic hydrocarbons, Z-tri-substituted olefines or contains three substituted olefine structural units, as 1,2-ethyl dicarboxylate-4-chloro-5,6, the polysubstituted aromatic hydrocarbons such as 7,8-naphthane, (the Z)-4-phenyl-4-p-methylphenyl-1-phenyl-3-thiazolinyl-Z-such as 1-alkynes tri-substituted olefines, vitamin A etc. contain the compound of three substituted olefine structural units.
The present invention also provides a kind of method of utilizing described cis-1-halogen-2-chloro-alkenes synthesise vitamins A, comprises step:
At first the compound shown in structural formula 13 is reacted to half an hour in-78 ℃ with tert-butyl lithium in organic solvent, then add Zinc Chloride Anhydrous to react half an hour at 0 ℃, then add tetra-triphenylphosphine palladium (Pd (PPh
3)
4) the 2-((1E shown in catalyzer and structural formula 12, the chloro-4-of 3Z)-3-bromo-1, the 3-butadienyl)-1,3, the 3-trimethyl cyclohexene was in 20 ℃-60 ℃ reactions 8 hours-12 hours, add again after zinc methide in 40 ℃-60 ℃ reactions 3 hours-5 hours, finally add tetrabutyl fluoride amine to stir 1.5 hours-3 hours in 15 ℃-38 ℃, make vitamin A through aftertreatment;
Compound shown in described structural formula 13 can adopt commercially available prod also can adopt existing preparation method's preparation, if adopted de Lera A.R.et.al, and Tetrahedron Lett.1992, preparation method's preparation of record in 33,6205.
2-((1E shown in described structural formula 12, the bromo-1,3-butadiene base of the chloro-4-of 3Z)-3-)-1,3, the 3-trimethyl cyclohexene belongs to cis of the present invention-1-halogen-2-chloro-alkenes, can adopt preparation method's preparation of cis of the present invention-1-halogen-2-chloro-alkenes.
Described organic solvent can be selected this area reaction system organic solvent commonly used, is preferably anhydrous tetrahydro furan.
Described tert-butyl lithium preferably adds with the form of the pentane solution of tert-butyl lithium, to reach better reaction effect.
Described zinc methide preferably adds with the form of the toluene solution of zinc methide, to reach better reaction effect.
Described tetrabutyl fluoride amine preferably adds with the form of the tetrahydrofuran solution of tetrabutyl fluoride amine, to reach better reaction effect.
The present invention has following advantage:
The stereochemistry of cis of the present invention-1-halogen-2-chloro-alkenes is cis, can be used for preparing polysubstituted aromatic hydrocarbons, Z-tri-substituted olefines or contain cis-or the compound of trans-tri-substituted olefine structural units, for polysubstituted aromatic hydrocarbons, Z-tri-substituted olefines or the synthetic effective way that provides of pharmaceutical intermediate and the natural product of three substituted olefine structural units is provided.
Preparation method of the present invention, the palladium of take is catalyzer, the connection alkene ester shown in formula II of take is additive, just can make alkynes halogen generation area and stereoselective reaction in acetic aid medium, thereby high productivity obtains cis-1-halogen-2-chloro-alkenes Compound I.Because reaction does not have trans-isomer(ide) to generate, reaction has almost 100% Atom economy, also avoided simultaneously the separation and purification process of traditional halogenating reaction complexity, reduced " three wastes " discharge, reduced environmental pollution, economic benefit and social benefit are all very remarkable, are a kind of simply efficient, eco-friendly methods.
Embodiment
Embodiment 1:
In the round-bottomed flask of 10mL, add lithium chloride (26mg, 0.6mmol) and palladium (5.6mg, 0.025mmol), add the 1mL acetate dissolution, then add the connection alkene ester (17.4mg, 0.1mmol) shown in phenylacetylene chlorine (73mg, 0.5mmol) and formula II.Reaction system adds the 5mL shrend 60 ℃ of reactions after 5 hours goes out, ethyl acetate (10mL) extraction three times.After organic phase merges with sodium hydrogen carbonate solution wash with the saturated common salt washing after the organic layer that obtains through anhydrous sodium sulfate drying, rotary evaporation is except desolventizing again, then use silica gel (300-400 order) column chromatography for separation (elutriant: sherwood oil) obtain cis-1,2-dichlorostyrene 71mg (productive rate: 82%), be colourless liquid.
Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.70 (s, 1H), 7.38-7.40 (m, 3H), 7.53-7.55 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 116.1,126.6 (2C), 128.7 (2C), 129.5,135.6,135.8; MS (EI, m/z): 176 (8), 174 (60), 172 (M
+, 90), 139 (28), 137 (M
+-
35Cl, 100).Show that colourless liquid is cis-1 shown in structural formula 3a, the chloro-2-vinylbenzene of 2-bis-.
Embodiment 2:
Except the palladium of 0.01mmol replaces the palladium of 0.025mmol in embodiment 1, make catalyzer, all the other operation stepss, with embodiment 1, obtain cis-1, the 2-dichlorostyrene, and productive rate 81%, the Characterization of The Products data are with embodiment 1.
Embodiment 3:
Except the phenylacetylene chlorine with in 4-fluorobenzene acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 68%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.65 (s, 1H), 7.08 (t, J=8.4Hz, 2H), 7.50-7.54 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 115.7 (d, J=21.9Hz, 2C), 115.9 (d, J=1.6Hz, 1C), 128.5 (d, J=8.4Hz, 2C), 132.0 (d, J=3.3Hz, 1C), 134.6,162.8 (d, J=248.6Hz, 1C); MS (EI, m/z): 194 (6), 192 (38), 190 (M
+, 58), 157 (32), 155 (M
+-
35Cl, 100).Show that colourless liquid is the cis shown in structural formula 3b-1, the chloro-2-pfluorostyrene of 2-bis-.
Embodiment 4:
Except the phenylacetylene chlorine with in 4-chlorobenzene acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 82%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.70 (s, 1H), 7.36 (d, J=8.4Hz, 2H), 7.47 (d, J=8.4Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 116.6,127.8 (2C), 128.8 (2C), 134.2,134.6,135.5; MS (EI, m/z): 210 (20), 208 (70), 206 (M
+, 75), 175 (10), 173 (60), 171 (M
+-
35Cl, 100), 138 (24), 136 (75).Show that colourless liquid is the cis shown in structural formula 3c-1, the chloro-2-of 2-bis-is to chloro-styrene.
Embodiment 5:
Outside the phenylacetylene chlorine with in 2,5-dichlorobenzene acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 90%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.52 (s, 1H), 7.27-7.34 (m, 2H), 7.46 (d, J=2.0Hz, 1H);
13C-NMR (CDCl
3, 100MHz): δ 120.6,127.3, and 130.0,130.9,131.9,133.8,134.1,136.2; MS (EI, m/z): 244 (38), 242 (80), 240 (M
+, 65), 209 (28), 207 (90), 205 (M
+-
35Cl, 100), 174 (10), 172 (60), 170 (94); Anal.Calcd.for C
8H
4Cl
4, HRMS:Cacl.239.9067, Found:239.9065.Show that colourless liquid is the cis shown in structural formula 3d-1, the chloro-2-of 2-bis-(2 ', 5 '-dichlorobenzene) base ethene.
Embodiment 6:
Except the phenylacetylene chlorine with in 4-bromobenzene acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 73%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.71 (s, 1H), 7.40 (d, J=8.6Hz, 2H), 7.51 (d, J=8.6Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 116.7,123.7,128.0 (2C), 131.8 (2C), 134.7 (2C); MS (EI, m/z): 254 (44), 252 (100), 250 (M
+, 65), 138 (22), 136 (72).Show that colourless liquid is the cis shown in structural formula 3e-1, the chloro-2-of 2-bis-is to bromstyrol.
Embodiment 7:
Except the phenylacetylene chlorine with in 4-methylbenzene acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 85%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 2.38 (s, 3H), 6.66 (s, 1H), 7.19 (d, J=8.0Hz, 2H), 7.43 (d, J=8.0Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 21.2,115.2,126.5 (2C), 129.3 (2C), 133.0,135.7,139.6; MS (EI, m/z): 190.0 (7), 188.0 (50), 186.0 (M
+, 79), 153 (27), 151 (M
+-
35Cl, 80).Show that colourless liquid is the cis shown in structural formula 3f-1, the chloro-2-p-methylstyrene of 2-bis-.
Embodiment 8:
Except the phenylacetylene chlorine with in 4-isopropyl benzene acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 80%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 1.27 (d, J=7.2Hz, 6H), 2.90-2.97 (m, 1H), 6.66 (s, 1H), 7.24 (d, J=8.0Hz, 2H), 7.46 (d, J=8.0Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 23.8 (2C), 33.9,115.1,126.6 (2C), 126.7 (2C), 133.3,135.7,150.5; MS (EI, m/z): 216 (25), 214 (M
+, 40), 201 (60), 199 (M
+-CH
3, 80), 165 (5), 163 (80).Show that colourless liquid is the cis shown in structural formula 3g-1, the chloro-2-p-isopropyl of 2-bis-vinylbenzene.
Embodiment 9:
Except the phenylacetylene chlorine with in 4-anisole acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 81%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 3.84 (s, 3H), 6.59 (s, 1H), 6.90 (d, J=8.4Hz, 2H), 7.47 (d, J=8.4Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 55.4,114.0 (2C), 114.2,128.0 (2C), 128.3,135.4,160.5; MS (EI, m/z): 206 (3), 204 (24), 202 (M
+, 39), 169 (29), 167 (M
+-
35Cl, 100).Show that colourless liquid is the cis shown in structural formula 3h-1, the chloro-2-of 2-bis-is to methoxy styrene
Embodiment 10:
Outside the phenylacetylene chlorine with in 3,4-dimethoxy phenylacetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 72%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 3.90 (s, 3H), 3.91 (s, 3H), 6.60 (s, 1H), 6.84 (d, J=8.4Hz, 1H), 7.02 (d, J=2.0Hz, 1H), 7.09 (dd, J=8.4,2.0Hz, 1H);
13C-NMR (CDCl
3, 100MHz): δ 60.0 (2C), 109.7,110.8,114.5,119.5,128.6,135.4,148.8,150.1; MS (EI, m/z): 236 (10), 234 (62), 232 (M
+, 100), 199 (6), 197 (M
+-
35Cl, 18).Show that colourless liquid is the cis shown in structural formula 3i-1, the chloro-2-of 2-bis-(3 ', 4 '-the dimethoxy substituted benzene) base ethene.
Embodiment 11:
Except the phenylacetylene chlorine with in 2-thienyl acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 77%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.74 (s, 1H), 7.01-7.04 (m, 1H), 7.28-7.31 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 114.6,126.5, and 126.7,127.5,129.3,138.7; MS (EI, m/z): 182 (7), 180 (35), 178 (M
+, 53).Show that colourless liquid is the cis shown in structural formula 3j-1, the chloro-2-of 2-bis-(2 '-thiophene) base ethene.
Embodiment 12:
Except the phenylacetylene chlorine with in 3-benzyloxy propine chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 71%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 4.16 (s, 2H), 4.56 (s, 2H), 6.50 (s, 1H), 7.32-7.40 (m, 5H);
13C-NMR (CDCl
3, 100MHz): δ 71.5,72.3,117.4,127.9 (2C), 128.1,128.6 (2C), 133.3,137.1; Anal.Calcd.for C
10H
10Cl
2O, HRMS (ESI): Cacl.216.0109, Found:216.0105.Show that colourless liquid is the cis shown in structural formula 3k-1, the chloro-3-benzyloxy of 2-bis-propylene.
Embodiment 13:
Except the phenylacetylene chlorine with in 2-cyclohexenyl acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 61%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 1.57-1.60 (m, 2H), 1.67-1.71 (m, 2H), 2.18-2.20 (m, 4H);
13C-NMR (CDCl
3, 100MHz): δ 21.7,22.4, and 25.7,25.9,113.7,130.2,131.6,137.5; MS (EI, m/z): 180 (6), 178 (35), 176 (M
+, 50), 143 (38), 141 (M
+-
35Cl, 100). show that colourless liquid is the cis shown in structural formula 3l-1, the chloro-2-cyclohexenyl of 2-bis-ethene.
Embodiment 14:
Except the phenylacetylene chlorine with in trans-styryl acetylenechloride alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 51%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.51 (s, 1H), 6.79 (t, J=15.2Hz, 1H), 7.05 (d, J=15.2Hz, 1H), 7.30-7.39 (m, 3H), 7.44-7.46 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 118.7,122.9,127.0 (2C), 128.6,128.9 (2C), 132.9,135.2,135.8; Anal.Calcd.for C
10H
8Cl
2, HRMS (ESI): Cacl.198.0003, Found:198.0004.Show that colourless liquid is the cis shown in structural formula 3m-1, the trans styryl ethene of the chloro-2-of 2-bis-.
Embodiment 15:
Except the phenylacetylene chlorine with in 2-naphthyl acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 83%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.84 (s, 1H), 7.54-7.56 (m, 2H), 7.59-7.62 (m, 1H), 7.83-7.88 (m, 3H), 8.04 (s, 1H);
13C-NMR (CDCl
3, 100MHz): δ 116.4,123.6, and 126.5,126.9,127.1,127.7,128.4,128.5,132.9,133.0,133.5,135.8; MS (EI, m/z): 226 (2), 224 (12), 222 (M
+, 20), 189 (35), 187 (M
+-
35Cl, 100).Show that colourless liquid is the cis shown in structural formula 3n-1, the chloro-2-of 2-bis-(2 '-naphthyl) ethene.
Embodiment 16:
Except the phenylacetylene chlorine with in 1-naphthyl acetylene chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 80%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.59 (s, 1H), 7.46-7.61 (m, 2H), 7.57-7.61 (m, 2H), 7.92 (t, J=7.2Hz, 2H), 8.11 (d, J=8.4Hz, 1H);
13C-NMR (CDCl
3, 100MHz): δ 118.9,125.1 (2C), 126.5,127.0,127.7,128.5,130.4,131.0,133.7,133.8,134.0; MS (EI, m/z): 226 (5), 224 (31), 222 (M
+, 49), 189 (33), 187 (M
+-
35Cl, 100).Show that colourless liquid is the cis shown in structural formula 3o-1, the chloro-2-of 2-bis-(1 '-naphthyl) ethene.
Embodiment 17:
Except the phenylacetylene chlorine with in 1-certain herbaceous plants with big flowers alkynes chlorine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 80%, and product: colourless liquid, Z/E=11/1.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 0.89 (t, J=6.4Hz, 3H), 1.20-1.30 (m, 10H), 1.54-1.58 (m, 2H), 2.38 (t, J=7.2Hz, 2H), 6.14 (s, 1H);
13C-NMR (CDCl
3, 100MHz): δ 14.1,22.6, and 27.1,28.5,29.1,29.2,31.8,37.6,113.2,137.7.Show that colourless liquid is the cis shown in structural formula 3p-1, the chloro-2-n-octyl of 2-bis-ethene.
Embodiment 18:
Except the phenylacetylene chlorine with in cyclohexenyl acetylene bromine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 72%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 1.58-1.60 (m, 2H), 1.68-1.71 (m, 2H), 2.14-2.16 (m, 2H), 2.20-2.22 (m, 2H), 6.40 (t, J=4.0Hz, 1H), 6.53 (s, 1H);
13C-NMR (CDCl
3, 100MHz): δ 21.7,22.4, and 25.8,26.1,103.1,130.6,132.5,140.2; MS (EI, m/z): 224 (8), 222 (44), 220 (M
+, 34), 187 (23), 181 (M
+-
35Cl, 16).Show that colourless liquid is the chloro-2-cyclohexenyl of the bromo-2-of the cis-1-shown in structural formula 3q ethene.
Embodiment 19:
Except the phenylacetylene chlorine with in phenylacetylene bromine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 80%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.89 (s, 1H), 7.38-7.41 (m, 3H), 7.54-7.57 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 105.3,126.7 (2C), 128.7 (2C), 129.5,136.5,138.5; MS (EI, m/z): 220 (25), 218 (100), 216 (M
+, 84), 183 (38), 181 (M
+-
35Cl, 36).Show that colourless liquid is the bromo-2-chloro-styrene of the cis-1-shown in structural formula 3r.
Embodiment 20:
Except using the phenylacetylene chlorine in fluorobenzene acetylene bromine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 76%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.83 (s, 1H), 7.05-7.09 (m, 2H), 7.51-7.55 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 105.1 (d, J=1.6Hz, 2C), 115.7 (d, J=21.8Hz, 1C), 128.6 (d, J=8.4Hz, 2C), 132.7,134.6,163.6 (d, J=248.6Hz, 1C); MS (EI, m/z): 238 (22), 236 (88), 234 (M
+, 70), 201 (39), 199 (M
+-
35Cl, 41).Show that colourless liquid is the chloro-2-pfluorostyrene of the bromo-2-of the cis-1-shown in structural formula 3s.
Embodiment 21:
Except using the phenylacetylene chlorine in methylbenzene acetylene bromine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 81%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 2.38 (s, 3H), 6.83 (s, 1H), 7.19 (d, J=8.0Hz, 2H), 7.44 (d, J=8.0Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 21.2,104.2,126.5 (2C), 129.2 (2C), 133.7,138.5,139.6; MS (EI, m/z): 229 (22), 227 (100), 225 (M
+, 79), 192 (39), 190 (M
+-
35Cl, 35).Show that colourless liquid is the chloro-2-p-methylstyrene of the bromo-2-of the cis-1-shown in structural formula 3t.
Embodiment 22:
Outside the phenylacetylene chlorine with in 3,4-dimethoxy phenylacetylene bromine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 77%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 3.89 (s, 3H), 3.90 (s, 3H), 6.76 (s, 1H), 6.83 (d, J=8.4Hz, 1H), 7.03 (d, J=1.6Hz, 1H), 7.10 (dd, J=8.4,1.6Hz, 1H);
13C-NMR (CDCl
3, 100MHz): δ 59.9 (2C), 103.6,109.8,110.8,119.7,129.4,138.2,148.8,150.1; MS (EI, m/z): 280 (25), 278 (100), 276 (M
+, 80), 263 (34), 261 (M
+-
35Cl, 28).Show colourless liquid be the chloro-2-of the bromo-2-of the cis-1-shown in structural formula 3u (3 ', 4 '-dimethoxy benzene)-ethene.
Embodiment 23:
Except using the phenylacetylene chlorine in chlorobenzene acetylene bromine alternate embodiment 1, all the other operation stepss are with embodiment 1, productive rate: 85%, and product: colourless liquid.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.89 (s, 1H), 7.35 (d, J=6.8Hz, 2H), 7.48 (d, J=6.8Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 105.8,127.9 (2C), 128.8 (2C), 135.0,135.5,137.4; MS (EI, m/z): 254 (30), 252 (70), 250 (M
+, 44), 219 (9), 217 (38), 214 (M
+-
35Cl, 30), 138 (32), 136 (M
+-
35Cl-
79Br, 100).Show that colourless liquid is that the chloro-2-of the bromo-2-of the cis-1-shown in structural formula 3v is to chloro-styrene.
Synthesizing of application examples 1, polysubstituted phenyl ring-naphthane skeleton
From 1,2-dihalo-1, the 3-diene sets out, and can successfully synthesize polysubstituted aromatic hydrocarbons skeleton in conjunction with Diels-Alder reaction and aromatization.
For example, from the compound shown in the structural formula 3l of embodiment 13 preparations, add the tetrolic acid diethyl ester in dimethylbenzene, to reflux 2 hours, the mol ratio of the compound shown in structural formula 3l and tetrolic acid diethyl ester is 1: 1.1, has just successfully obtained compound 4.This explanation 1,2-dihalo-1,3-diene can be used as a kind of new Diels-Alder reaction diene body.
Concrete operation step is as follows:
In the reaction flask of 25mL, add the compound (84mg, 0.5mmol) shown in structural formula 3l and tetrolic acid diethyl ester (93.5mg, 0.55mmol), use the 1mL xylene soluble.Reaction system was 120 ℃ of reactions 8 hours, cooling, directly rotary evaporation, except desolventizing, is then used silica gel (300-400 order) column chromatography for separation (elutriant: petrol ether/ethyl acetate=5/1, volume ratio) (productive rate: 66%) compound 4, are colourless liquid to obtain 103mg.Colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 1.33-1.38 (m, 6H), 1.75-1.81 (m, 4H), 2.72-2.75 (m, 2H), 2.78-2.81 (m, 2H), 4.31 (q, J=7.2Hz, 2H), (4.39 q, J=7.2Hz, 2H), 7.83 (s, 1H);
13C-NMR (CDCl
3, 100MHz): δ 14.1,14.2, and 21.9,22.0,26.7,28.0,61.5,61.6,125.9,127.7,134.3,135.5,136.6,140.7,164.7,168.8; Anal.Calcd.for C
16H
19ClO
4, HRMS (ESI): Cacl.310.0972, Found:310.0970.Show that this colourless liquid is 1 shown in structural formula 4,2-ethyl dicarboxylate-4-is chloro-5,6,7, the 8-naphthane.
The selectivity of application examples 2, Z-tri-substituted olefines is synthetic
By the trickle regulation and control to reaction conditions, can realize the difference of C-Cl and C-Br chemical bonding reaction activity, thereby realize itself and metal reagent (R
1M) selectivity of coupling, then pass through coupling (R for the second time
2M) reaction just can be synthesized Z-tri-substituted olefines, and diagram is as follows:
This is studied to discovery, by simple optimization, the carbon in the compound shown in the structural formula 3q of embodiment 18 preparations-bromine key and carbon-chlorine key can be at Pd (PPh
3)
2Cl
2(5mol%) and CuI (15mol%) the selectivity coupling that realizes carbon-bromine key under existing with 81% productive rate, obtain compound 5, further the Suzuki linked reaction can obtain with good productive rate Z-tri-substituted olefines 6, and the two keys in its product and triple bond can further change into other functional group.
Reaction conditions: a=phenylacetylene, Pd (PPh
3)
2Cl
2, CuI, Et
3N, 80 ℃ of toluene; B=Pd (OAc)
2, PPh
3, p-Me-C
6H
4B (OH)
2(to methylphenylboronic acid), Cs
2CO
3, Isosorbide-5-Nitrae-dioxy six alkane, 90 ℃.
Concrete operation step is as follows:
In the reaction flask of 25mL, add the compound (103mg, 0.5mmol) shown in structural formula 3q, Pd (PPh
3)
2Cl
2(16.6mg, 0.05mmol), CuI (14.5mg, 0.075mmol) and Et
3N (0.17mL, 1.5mmol), phenylacetylene (0.16mL, 1.0mmol), add 1mL toluene and dissolve.Reaction system, 80 ℃ of reactions 10 hours, adds the 5mL shrend and goes out, ethyl acetate (10mL) extraction three times.After organic phase merges with sodium hydrogen carbonate solution wash with the saturated common salt washing after the organic layer that obtains through anhydrous sodium sulfate drying, rotary evaporation is except desolventizing again, then (elutriant: (productive rate: 81%) compound 5, are colourless liquid sherwood oil) to obtain 97mg to use silica gel (300-400 order) column chromatography for separation.This colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 6.48 (s, 1H), 7.36-7.38 (m, 3H), 7.40-7.42 (m, 3H), 7.55-7.57 (m, 2H), 7.67-7.69 (m, 2H);
13C-NMR (CDCl
3, 100MHz): δ 86.1,97.9,107.1,123.0,126.3 (2C), 128.4 (2C), 128.5 (2C), 128.6,129.6,131.7 (2C), 136.6,143.9; MS (EI, m/z): 240 (25), 238 (M
+, 71), 203 (M
+-
35Cl, 55), 101 (28); Anal.Calcd.for C
16H
11Cl, HRMS (EI): Cacl.238.0549, Found:238.0549.Show that this colourless liquid is compound shown in structural formula 5.
In the reaction flask of 25mL, add compound 5 (120mg, 0.5mmol), Pd (OAc)
2(11.2mg, 0.05mmol), PPh
3 (52.4mg, 0.2mmol), CsC
2O
3(448mg, 1.5mmol) and to methylphenylboronic acid (136mg, 1.0mmol), add 1mL1, and 4-dioxy six alkane dissolve.Reaction system, 90 ℃ of reactions 10 hours, adds the 5mL shrend and goes out, ethyl acetate (10mL) extraction three times.Organic phase is washed with saturated common salt and is washed with sodium hydrogen carbonate solution after merging, the organic layer obtained is through anhydrous sodium sulfate drying, rotary evaporation is except desolventizing again, then (elutriant: (productive rate: 70%) compound 6, are colourless liquid sherwood oil) to obtain 103mg to use silica gel (300-400 order) column chromatography for separation.This colourless liquid
1H-NMR (CDCl
3, 400MHz): δ 2.43 (s, 3H), 6.19 (s, 1H), 7.23 (d, J=8.0Hz, 2H), 7.28-7.30 (m, 3H), 7.31-7.34 (m, 7H), 7.47 (d, J=8.0Hz, 2H);
13C-NMR (CDCl
3, 100MHz): δ 21.4,89.3,93.5,106.6,123.7,127.9,128.1 (2C), 128.2 (5C), 128.4 (2C), 130.1 (2C), 131.4 (2C), 136.2,138.1,141.8,152.6; Anal.Calcd.for C
23H
18, HRMS (ESI): Cacl.294.1409, Found:294.1403.Show that this colourless liquid is (the Z)-4-phenyl shown in structural formula 6-4-p-methylphenyl-1-phenyl-3-thiazolinyl-1-alkynes.
Application examples 3, the present invention are in the synthetic method of the medicine intermediate that contains three substituted olefines or the synthetic utilization-new vitamin A of natural product.
Z-tri-substituted olefines extensively exist in the natural product with physiologically active or medicine intermediate.For example, has the natural product 7 of antitumour activity (to KB3.1 cell, IC
50For 40pg/mL) and natural product 8 (to KB cell, IC
50For 10pg/mL) its crucial structural unit is exactly two Z-tri-substituted olefines.Vitamin A with different physiological roles contains a plurality of Z-tri-substituted olefine segments equally.In addition, the Macrolide natural product 9 with 4 Z-, tri-substituted olefine structural units is cell cycle regulations, suppresses the external secretion type cytotoxin that dendritic cell vaccination is replied, and can be used as a kind of neotype immunosuppressant.10 its synthetic difficult points of the natural product with cancer therapy drug activity of recent findings are also to be to build its a plurality of Z-tri-substituted olefine structural units.This structural unit is also at macrolide antibiotics mibemycin β
3Deng extensively existence in natural product and pharmaceutical intermediate.
As everyone knows, to healthy pay attention to day by day, society is increasing to the demand of vitamin A along with people, and original separation and extraction technology can not meet human wants far away.Therefore, synthesise vitamins A has become a urgent task simply and effectively, obviously, it not only has good economic benefit, have more important social benefit, so the utilization in synthetic is studied at pharmaceutical intermediate and natural product to the present invention to choose vitamin A and be target.From alkynes bromine compounds 11s, use the present invention to obtain the bromo-2-chloro-alkenes of cis 1-compound 12; through twice cross-coupling reaction deprotection base, just obtained vitamin A again; obviously this provides a new synthetic route for vitamin A synthetic, is conducive to the exploitation of vitamin A synthesis technique of future generation.Diagram is as follows:
Concrete implementation step is as follows:
Except the phenylacetylene chlorine with in compound 11 alternate embodiments 1, all the other operation stepss are with embodiment 1, productive rate: 60%, and product: weak yellow liquid.Weak yellow liquid
1H-NMR (CDCl
3, 400MHz): δ 1.02 (s, 6H), 1.45-1.48 (m, 2H), 1.58-1.64 (m, 2H), (1.69 s, 3H), 1.99-2.02 (m, 2H), 6.09 (d, J=17.2Hz, 1H), 6.51 (s, 1H), 6.66 (d, J=17.2Hz, 1H);
13C-NMR (CDCl
3, 100MHz): δ 19.1,21.7,28.3 (2C), 33.0,34.2,39.4,106.2,127.6,131.2,132.7,136.5,138.1; Anal.Calcd.for C
13H
18BrCl, HRMS (ESI): Cacl.288.0280, Found:288.0281.Show that this weak yellow liquid is the 2-shown in structural formula 12 (the bromo-1,3-butadiene base of the chloro-4-of (1E, 3Z)-3-)-1,3, the 3-trimethyl cyclohexene.
In the reaction flask of 25mL, add compound 13 (203mg, 0.6mmol), with the 1mL anhydrous tetrahydro furan, dissolve, at-78 ℃ of tert-butyl lithium pentane solution 1.2mL that add 1.5mol/L (M), reaction adds Zinc Chloride Anhydrous (96mg) after half an hour, then after 0 ℃ of reaction half an hour, add compound 12 (145mg, 0.5mmol), Pd (PPh
3)
4(29mg, 0.0025mmol), reaction system was room temperature reaction 10 hours.Then the toluene solution 0.5mL that adds the zinc methide of 1.0M in reaction system, reaction system adds the tetrahydrofuran solution 0.7mL of tetrabutyl fluoride amine 1.0M 50 ℃ of reactions after 3 hours, the reaction system stirring at room is cooling after 2 hours, add the 5mL shrend and go out, ethyl acetate (10mL) extraction three times.Organic phase is washed with ammonium chloride solution and saturated common salt after merging in succession, the organic layer obtained is through anhydrous sodium sulfate drying, rotary evaporation is except desolventizing again, then (elutriant: (productive rate: 64%) vitamin A is colourless liquid petrol ether/ethyl acetate=5/1) to obtain 91mg to use silica gel (300-400 order) column chromatography for separation.This colourless liquid
1H-NMR (400MHz, CDCl
3) 1.05 (s, 6H), 1.41-1.53 (m, 2H), (1.52-1.65 m, 2H), 1.72 (s, 3H), (1.89 s, 3H), 1.98 (s, 3H), (2.01 t, J=6.0Hz, 2H), 4.31 (d, J=6.8Hz, 2H), 5.69 (t, J=6.8Hz, 1H), 6.10 (d, J=16.0Hz, 1H), (6.14 d, J=11.2Hz, 1H), 6.17 (d, J=16.0Hz, 1H), 6.29 (d, J=15.2Hz, 1H), 6.60 (dd, J=15.2,11.0Hz, 1H);
13C-NMR (100MHz, CDCl
3) δ 12.7,12.8,19.2,21.7,28.9,33.1,34.2,39.6,59.5,125.3,126.8,129.4,129.9,130.1,136.4,136.4,136.9,137.6,137.8; Show that this colourless liquid is vitamin A.
In sum, the present invention utilizes the proton solution reaction of palladium catalysis to realize a synthetic route for preparing cis-1-halogen-2-chloro-alkenes from alkynes halogen selectivity.This cis-1-halogen-2-chloro-alkenes compound can synthesize polysubstituted aromatic hydrocarbons smoothly in conjunction with the Diels-Alder reaction.The more important thing is, pass through cross-coupling reaction, this cis-1-halogen-2-chloro-alkenes compound can be transformed into more difficult synthetic Z-tri-substituted olefine segments in organic synthesis, thereby provides effective way for pharmaceutical intermediate and the natural product that contains three substituted olefine structural units.On this basis, we have found a new vitamin A synthetic method, provide technical support for developing its synthesis technique of future generation.
Claims (3)
1. the preparation method of cis-1-halogen-2-chloro-alkenes comprises step:
Palladium and lithium chloride are dissolved in acetic acid, add the connection alkene ester shown in the compound shown in formula II I and formula II as reaction system, 40 ℃-60 ℃ react completely after, through aftertreatment, make structural formula cis as described as I-1-halogen-2-chloro-alkenes;
I, in the formula I, R is phenyl, monosubstituted phenyl, di-substituted-phenyl, tri-substituted phenyl, 1-naphthyl, 2-naphthyl, thienyl, furyl, thiazolinyl, benzyloxy methylene radical, alkyl or heteroatoms substituted alkyl; X is chlorine atom or bromine atoms;
Substituting group on described monosubstituted phenyl, di-substituted-phenyl or tri-substituted phenyl is alkyl, alkoxyl group, fluorine atom, chlorine atom or bromine atoms; Substituting group on di-substituted-phenyl or tri-substituted phenyl is identical or different;
Described thiazolinyl is C
2-C
20A kind of in alkylene;
Described alkyl is C
1-C
20Alkyl in a kind of;
Described heteroatoms substituted alkyl is the C that N, S, P or O heteroatoms replace
1-C
20Alkyl in a kind of;
Described alkoxyl group is C
1-C
20Alkoxyl group in a kind of;
Bn in formula II is benzyl;
2. the preparation method of cis according to claim 1-1-halogen-2-chloro-alkenes, it is characterized in that, the mol ratio of the compound shown in connection alkene ester, lithium chloride and the formula II I shown in described palladium, formula II is 0.02-0.05:0.1-0.3:1-2:1.
3. the preparation method of cis according to claim 1-1-halogen-2-chloro-alkenes, is characterized in that, 60 ℃ of reactions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100047579A CN102531830B (en) | 2012-01-09 | 2012-01-09 | Cis-1-halo-2-chloroalkene and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100047579A CN102531830B (en) | 2012-01-09 | 2012-01-09 | Cis-1-halo-2-chloroalkene and preparation method and application thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310350098.9A Division CN103396350B (en) | 2012-01-09 | 2012-01-09 | Method for synthesizing vitamin A from cis-1-halo-2-chloroolefine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102531830A CN102531830A (en) | 2012-07-04 |
| CN102531830B true CN102531830B (en) | 2013-11-27 |
Family
ID=46340022
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100047579A Expired - Fee Related CN102531830B (en) | 2012-01-09 | 2012-01-09 | Cis-1-halo-2-chloroalkene and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102531830B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104876820A (en) * | 2015-04-22 | 2015-09-02 | 郑校昆 | Method for catalysis synthesizing of aryl formic ether compound |
-
2012
- 2012-01-09 CN CN2012100047579A patent/CN102531830B/en not_active Expired - Fee Related
Non-Patent Citations (13)
| Title |
|---|
| A.V.Martynov et al.,.Chlorobromination of phenylacetylene with the SnCl4-Br2 System.《Russian Journal of general chemistry》.2005,第75卷(第11期),1840-1841. |
| Akio Minato et al..remarkable steric effect in palladium-catalyzed gringnard coupling：regio- and stereoselective monoalkylation and –arylation of 1,1-dichloro-1-alkene.《J.Am.Chem.Soc》.1987,第109卷第1257-1258页. * |
| Chlorobromination of phenylacetylene with the SnCl4-Br2 System;A.V.Martynov et al.,;《Russian Journal of general chemistry》;20051231;第75卷(第11期);第1840-1841页 * |
| Decomposition of perchloric acid in dilute solutions by meta- and para-substituted phenylacetylenes.Reaction mechanisms;Jean-pierre montheard et al.,;《J.CHEM.RESEARCH》;19831231(第9期);第224-225页 * |
| Jacques Kagan et al.,.Reaction of phosphorus pentachloride with 2-acetylthiophene and acetophenone.《J.Org.Chem》.1983,第48卷第703-706页. |
| Jean-pierre montheard et al.,.Decomposition of perchloric acid in dilute solutions by meta- and para-substituted phenylacetylenes.Reaction mechanisms.《J.CHEM.RESEARCH》.1983,(第9期),第224-225页. |
| Keith Yates et al.,.Vinyl cation intermediates in electrophilic additions to triple bonds.1.chlorination of arylacetylenes.《J.Org.Chem》.1980,第45卷第2377-2384页. |
| Keresslidze R.V et al.,.Synthesis of dichlorovinyl derivatives of naphthalene.《Lzv.Akad.Nauk Gruz.SSR,Ser.Khim》.1990,第16卷(第2期),152-154. |
| Masahito Ochiai et al.,.Synthesis of (Z)-1,2-dihalo-1-alkenes by the reaction of （Z）-(β-halovinyl)phenyliodonium salts with n-Bu4NX or KX/CuX.Competitions between nucleophilic vinylic substitutions and aromatic substitutions.《Chemistry Letters》.1994,871-874. * |
| Reaction of phosphorus pentachloride with 2-acetylthiophene and acetophenone;Jacques Kagan et al.,;《J.Org.Chem》;19831231;第48卷;第703-706页 * |
| Ryuichi Tanaka et al.,.Nucleophilic attack on halogeno(pheny)acetylene by halide ions.《J.C.S.Perkin II》.1980,1714-1720. * |
| Synthesis of dichlorovinyl derivatives of naphthalene;Keresslidze R.V et al.,;《Lzv.Akad.Nauk Gruz.SSR,Ser.Khim》;19901231;第16卷(第2期);第152-154页 * |
| Vinyl cation intermediates in electrophilic additions to triple bonds.1.chlorination of arylacetylenes;Keith Yates et al.,;《J.Org.Chem》;19801231;第45卷;第2377-2384页 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104876820A (en) * | 2015-04-22 | 2015-09-02 | 郑校昆 | Method for catalysis synthesizing of aryl formic ether compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102531830A (en) | 2012-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wu et al. | Geminal bis (boron) compounds: their preparation and synthetic applications | |
| Yu et al. | Iron salt, a cheap, highly efficient and environment-friendly metal catalyst for Se–Se bond cleavage and the further reaction with methylenecyclopropanes under mild conditions | |
| Ohara et al. | Cycloaddition of styrene derivatives with quinone catalyzed by ferric ion; remarkable acceleration in an ionic liquid solvent system | |
| CN104592019B (en) | The method for preparing (E) -2- isopropyl -5- methyl -2,4- hexadienyl acetic acid esters | |
| CN101624390A (en) | Preparation method of key intermediate of rosuvastatin calcium side chain | |
| Sekine et al. | Enantioselective Functionalization of Difluorocyclopropenes Catalyzed by Chiral Copper Complexes: Proposal for Chiral gem-Dimethyl and tert-Butyl Analogues | |
| CN107417582B (en) | A kind of preparation method of E- alkenyl sulfone compound | |
| CN102531830B (en) | Cis-1-halo-2-chloroalkene and preparation method and application thereof | |
| CN101671242B (en) | Method for synthesizing trans-4-(trans-4'-alkyl cyclohexyl) cyclohexanal | |
| CN102633836B (en) | Method for synthesizing bis(diphenylphosphino)-alkane | |
| CN104829465B (en) | A kind of preparation method of 4- isopropylaminos-n-butyl alcohol | |
| CN108976243A (en) | Spiral shell-chroman -4,3 '-Oxoindole synthetic method is synthesized with the hydroxy-benzyl alcohol of neighbour containing Oxoindole by dimethyl furan | |
| CN103396350B (en) | Method for synthesizing vitamin A from cis-1-halo-2-chloroolefine | |
| CN103694153B (en) | The method of styracin and arylsulfinate Reactive Synthesis alkenyl sulfone compound | |
| CN113262822A (en) | N-heterocyclic carbene metal palladium complex catalyst, and synthesis method and application thereof | |
| CN115010600B (en) | Method for synthesizing polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction | |
| CN107827927A (en) | A kind of method that nickel catalyzes and synthesizes phosphoric acid safe ground azoles profit | |
| CN106928047A (en) | A kind of synthetic method of blood lipid-lowering medicine ciprofibrate | |
| WO2001057046A1 (en) | Method of converting functional group through halogen-metal exchange reaction | |
| Ranu et al. | Chemo-, regio-and stereoselective addition of triorganoindium reagents to acetates of Baylis–Hillman adducts: a new strategy for the synthesis of (E)-and (Z)-trisubstituted alkenes | |
| CN105348037A (en) | Synthetic method of directly coupling aryl halide by aromatic hydrocarbon Grignard reagent in the presence of recycled modified palladium-charcoal | |
| CN108863777A (en) | A method of preparing oxalate | |
| CN114560892A (en) | Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof | |
| CN105175392A (en) | Carboxylic acid compounds containing thiophene structures and amide compounds containing thiophene structures and preparation method for carboxylic acid compounds and amide compounds | |
| CN114907246A (en) | Total synthesis method of vitamin A, derivative thereof and deuterated compound thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20131127 Termination date: 20170109 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |